This invention relates to a process for treating a patient having a malignant tumor by activating human blood mononuclear cells of the patient and infusing them back into the patient.
A type of cancer treatment, termed adoptive immunotherapy, is based on the infusion into the patient of immunoreactive lymphocytes that generate an anti-tumor immune response. Unfortunately, the toxicity that accompanies the conventional approach to this therapy is substantial, and in combination with the high cost, raises serious doubts concerning the feasibility and practical application of this treatment. We have developed a novel approach to adoptive immunotherapy in order to make it a more feasible and cost-effective treatment. Our approach to adoptive immunotherapy is based upon the effective specific immunization of the patient by the tumor through the in vitro immunization of the patient's own peripheral blood lymphocytes followed by the infusion back into the patient of these in vitro immunized cells. In vitro immunization can be more effective than conventional in vivo immunization since it allows for the tight control of several variables that might be critical to the immunization process, including antigen concentration, duration of antigen exposure, method of antigen presentation, depletion or enrichment from within the total population of cells to be immunized of various lymphocyte subsets and the presence of lymphokines and other immunomodulators in the immunizing cultures.
In U.S. patent Ser. No. 407,236, filed Aug. 11, 1982, now abandoned and its continuation Ser. No. 696,546 filed Jan. 30, 1985, now U.S. Pat. No. 4,711,611 both by Osband et al., a procedure is disclosed for producing antibodies and immunoreactive lymphocytes by exposing in vitro the mononuclear cells of a patient to an antigen to which the patient had not been exposed previously (primary immunization). While methods have been described previously which allow for the immunization of mononuclear cells to an antigen to which the person was exposed previously (secondary immunization), the process for primary in vitro immunization that is described in these applications is optimal as well for secondary immunization/activation, and the cells that result are suited for subsequent therapeutic use by their infusion into the patient.
It would be highly desirable to provide a process for producing immunoreactive lymphocytes against a patient's tumor that does not threaten the patient's health. Furthermore, it would be desirable to provide such a process in which continuous cell lines can be formed so that cell or cell products, including antibody, can be obtained continuously over a long period of time so that the patient can be treated with the cells or cell products.